This program, which began more than 39 years ago, brings together investigators from multiple disciplines with an interest in the integrative control of circulatory function. Our major long-term goal has been to develop a quantitative analysis of cardiovascular (CV) dynamics and related control systems, including the kidneys, sympathetic nervous system (SNS), and endocrine systems. Two unique features of this program are: 1) it utilizes an integrative approach to understand complex interactions between multiple components of CV control systems, and 2) it focuses mainly on long-term control of the circulation because many CV diseases, such as hypertension, are manifestations of abnormal control mechanisms that develop slowly over long periods of time. The research proposed in this application is described by the titles of the projects as follows: I. Neurohumoral and Renal Mechanisms of Hypertension; this project will elucidate the neurohumoral mechanisms, central nervous system (CMS) circuits and signaling pathways that mediate obesity induced SNS activation, impaired renal-pressure natriuresis and hypertension. II. Renal Control of Body Fluid Volumes and Circulatory Dynamics; this project will determine the role of factors released by the placenta in causing endothelial dysfunction, impaired renal-pressure natriuresis and hypertension during chronic reductions in uterine perfusion pressure in pregnant rats. III. (previously Project V) Hormonal Mechanisms of Postmenopausal Hypertension; this project will test the hypothesis that post-menopausal hypertension is mediated by increases in 20-HETE and/or increases in preglomerular vascular sensitivity to 20-HETE and that androgens increase 20-HETE by increasing expression of CYP4A2 and by increasing intrarenal Ang II and endothelin. IV. Neural Mechanisms in Cardiorenal Regulation; this project will use sophisticated techniques in chronically instrumented dogs to determine whether the CMS plays an important role in chronic resetting of the baroreflex and whether chronic activation of the baroreflex has sustained effects to inhibit renal sympathetic nerve activity, promote sodium excretion and reduce arterial pressure. The total program, including core support services, provides a unique interdisciplinary approach toward developing an integrative analysis of long-term regulation of blood pressure and circulatory dynamics in several forms of experimental hypertension that have great relevance to human hypertension. (End of Abstract)